Verteporfin, a suppressor of YAP-TEAD complex, presents promising antitumor properties on ovarian cancer

被引:125
作者
Feng, Juntao [1 ]
Gou, Jinhai [1 ]
Jia, Jia [1 ]
Yi, Tao [2 ]
Cui, Tao [1 ]
Li, Zhengyu [1 ,2 ]
机构
[1] Sichuan Univ, Dept Gynecol & Obstet, Chengdu, Peoples R China
[2] Sichuan Univ, West China Univ Hosp 2, Sichuan Key Lab Gynecol Oncol, Chengdu, Peoples R China
基金
中国国家自然科学基金;
关键词
YAP; CCN2; ovarian cancer; verteporfin; Hippo pathway; HIPPO PATHWAY; GROWTH; CELLS; SPHINGOSINE-1-PHOSPHATE; REGENERATION; COACTIVATOR; MIGRATION; PROTEIN;
D O I
10.2147/OTT.S109979
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Yes-associated protein (YAP) is a key transcriptional coactivator of Hippo pathway and has been shown to be an oncoprotein in ovarian cancer (OC). Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has been recently proven to be a suppressor of YAP-TEAD complex and has shown potential in anticancer treatment. In this study, we aimed to explore the potential effect of VP in the treatment of OC. Our results showed that VP led to inhibition of proliferation in a time-and dose-dependent manner and to the suppression of migratory and invasive capacities of OC cells. Western blot and real-time polymerase chain reaction demonstrated that VP induced YAP cytoplasmic retention and deregulated inducible YAP and CCNs in OC cells. In vivo, VP exerted a significant effect on tumor growth in OVCAR8 xenograft mice, resulting in tumor nodules with lower average weight and reduced volume of gross ascites. In addition, VP treatment remarkably upregulated cytoplasmic YAP and phosphorylation YAP and downregulated CCN1 and CCN2, but exerted little effect on YAP-upstream components in Hippo pathway. In conclusion, our results suggested that VP may be a promising agent for OC, acting by suppressing YAP-TEAD complex.
引用
收藏
页码:5371 / 5381
页数:11
相关论文
共 36 条
[1]   The role of the Hippo pathway in human disease and tumorigenesis [J].
Barron, Daniel A. ;
Kagey, Jacob D. .
CLINICAL AND TRANSLATIONAL MEDICINE, 2014, 3
[2]   The clinically used photosensitizer Verteporfin (VP) inhibits YAP-TEAD and human retinoblastoma cell growth in vitro without light activation [J].
Brodowska, Katarzyna ;
Al-Moujahed, Ahmad ;
Marmalidou, Anna ;
Horste, Melissa Meyer Zu ;
Cichy, Joanna ;
Miller, Joan W. ;
Gragoudas, Evangelos ;
Vavvas, Demetrios G. .
EXPERIMENTAL EYE RESEARCH, 2014, 124 :67-73
[3]   The role of LPA and YAP signaling in long-term migration of human ovarian cancer cells [J].
Cai, Hui ;
Xu, Yan .
CELL COMMUNICATION AND SIGNALING, 2013, 11
[4]   The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program [J].
Cai, Jing ;
Zhang, Nailing ;
Zheng, Yonggang ;
de Wilde, Roeland F. ;
Maitra, Anirban ;
Pan, Duojia .
GENES & DEVELOPMENT, 2010, 24 (21) :2383-2388
[5]   A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis [J].
Chen, Qian ;
Zhang, Nailing ;
Gray, Ryan S. ;
Li, Huili ;
Ewald, Andrew J. ;
Zahnow, Cynthia A. ;
Pan, Duojia .
GENES & DEVELOPMENT, 2014, 28 (05) :432-437
[6]   YAP activation protects urothelial cell carcinoma from treatment-induced DNA damage [J].
Ciamporcero, E. ;
Shen, H. ;
Ramakrishnan, S. ;
Ku, S. Yu ;
Chintala, S. ;
Shen, L. ;
Adelaiye, R. ;
Miles, K. M. ;
Ullio, C. ;
Pizzimenti, S. ;
Daga, M. ;
Azabdaftari, G. ;
Attwood, K. ;
Johnson, C. ;
Zhang, J. ;
Barrera, G. ;
Pili, R. .
ONCOGENE, 2016, 35 (12) :1541-1553
[7]   A review: molecular aberrations within Hippo signaling in bone and soft-tissue sarcomas [J].
Deel, Michael D. ;
Li, Jenny J. ;
Crose, Lisa E. S. ;
Linardic, Corinne M. .
FRONTIERS IN ONCOLOGY, 2015, 5
[8]   The Autophagy Inhibitor Verteporfin Moderately Enhances the Antitumor Activity of Gemcitabine in a Pancreatic Ductal Adenocarcinoma Model [J].
Donohue, Elizabeth ;
Thomas, Anitha ;
Maurer, Norbert ;
Manisali, Irina ;
Zeisser-Labouebe, Magali ;
Zisman, Natalia ;
Anderson, Hilary J. ;
Ng, Sylvia S. W. ;
Webb, Murray ;
Bally, Marcel ;
Roberge, Michel .
JOURNAL OF CANCER, 2013, 4 (07) :585-596
[9]   YAP regulates cell proliferation, migration, and steroidogenesis in adult granulosa cell tumors [J].
Fu, David ;
Lv, Xiangmin ;
Hua, Guohua ;
He, Chunbo ;
Dong, Jixin ;
Lele, Subodh M. ;
Li, David Wan-Cheng ;
Zhai, Qiongli ;
Davis, John S. ;
Wang, Cheng .
ENDOCRINE-RELATED CANCER, 2014, 21 (02) :297-310
[10]   Non-Photoinduced Biological Properties of Verteporfin [J].
Gibault, Floriane ;
Corvaisier, Matthieu ;
Bailly, Fabrice ;
Huet, Guillemette ;
Melnyk, Patricia ;
Cotelle, Philippe .
CURRENT MEDICINAL CHEMISTRY, 2016, 23 (11) :1171-1184